Assay for the detection of anti-idiotypic antibodies to monoclonal antibody B72.3.
The administration of xenogenic monoclonal antibodies (MAbs) leads in many cases to a host immune response represented by the generation of antibodies that can be directed against allotypic, isotypic, and idiotypic determinants present on the xenogeneic MAb. Anti-idiotypic antibodies (Ab2s) can be detected by measuring their specific reactivity in sandwich assays using their ability to cross-link labeled Ab1 to Ab1 attached to a solid phase; however, when the MAb used for these studies reacts with a multideterminant tumor-associated antigen found in the circulation (e.g., TAG-72), the utility of these anti-idiotype assays may be limited. To determine the levels of anti-idiotypic antibodies that could be detected in patients undergoing MAb B72.3-based immunodiagnostic and immunotherapeutic protocols, we investigated the ability of a solid-phase sandwich radioimmunoassay (RIA) to detect anti-idiotypic antibodies raised against B72.3. Furthermore, to overcome the interference of circulating TAG-72 and/or antibodies to allotypic and isotypic determinants in the evaluation of an anti-idiotypic response, we developed a methodology using CC49-coated resin to absorb the interfering molecules (CC49 is a second anti-TAG-72 MAb). Under the conditions established, all of the TAG-72 antigen was removed by adsorption with MAb CC49. Furthermore, since the treatment used an isotype-identical murine MAb, the binding due to the anti-mouse antibodies, other than the anti-idiotype, was completely abolished after a treatment with MAb CC49, leaving only the anti-idiotype component.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferroni
P
P
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Milenic
D E
DE
Schlom
J
J
Colcher
D
D
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis* / Q000096:biosynthesis; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology; D001665:Binding Sites; D001667:Binding, Competitive; D005069:Evaluation Studies as Topic; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D011863:Radioimmunoassay / Q000379:methods*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; C047052:tumor-associated antigen 72